Studies of the pathogenesis of feline immunodeficiency virus
The project had three aims: namely: - (i) to investigate the in vitro cell tropism of a range of field isolates from cats at different stages of disease and compare their phenotype with the well-characterised prototype viruses FIV-PET and FIV-GL8. (ii) to study the pathogenicity of these viruses in vivo in order to examine any correlation between virulence in vivo and tropism in vitro. (iii) to look at the role of the env gene in the pathogenicity of FIV. In vitro studies of cell tropism revealed that isolates from cats in the terminal stage of disease had a greater ability to utilise CXCR4 than isolates from cats displaying no clinical signs. In vivo, these symptomatic isolates, with greater CXCR4-tropism in vitro, displayed less virulence when compared with isolates from asymptomatic cats. Chimaeras were made by inserting the env genes of an isolate from the asymptomatic or terminal disease stages into a FIV-G8Mya backbone, allowing comparison of the cell tropism and receptor usage of these genes and the study of their phenotype with regard to virulence in vivo. The env genes from FIV-PET and the symptomatic isolate (F0827Hs) had a greater affinity to utilise CXCR4 for cell entry in vitro and this correlated with reduced virulence in vivo when compared to the asymptomatic isolate env and FIV-G8Mya. These studies highlight a trend where tropism in vitro can be correlated with virulence in vivo. Furthermore, the study indicated that viruses from asymptomatic cats (with a lesser ability to utilise CXCR4) have increased virulence. As these are the agents most likely to be transmitted in the field by the apparently healthy cat, vaccine development should focus on this population of viruses.